BioPAX pathway converted from "Diseases associated with N-glycosylation of proteins" in the Reactome database.Diseases associated with N-glycosylation of proteinsDiseases associated with N-glycosylation of proteinsCongenital disorders of glycosylation (CDGs) are a group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. These glycoconjugates play critical roles in processes such as metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity. CDGs are divided into 2 main groups: type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs comprise defects in the trimming and processing of protein-bound glycans (Marquardt & Denecke 2003, Grunewald et al. 2002, Hennet 2012, Cylwik et al. 2013).Authored: Jassal, B, 2013-06-28Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-06-28Defective ALG6 causes ALG6-CDG (CDG-1c)Defective ALG6 causes ALG6-CDG (CDG-1c)Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG6) normally adds the first glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins (Imbach et al. 1999). Defects in ALG6 can cause congenital disorder of glycosylation 1c (ALG6-CDG, CDG-1c; MIM:603147), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Imbach et al. 1999, Imbach et al. 2000, Westphal et al. 2000, Sun et al. 2005). ALG6 deficiency is accompanied by an accumulation of the N-glycan precursor (GlcNAc)2 (Man)9 (PP-Dol)1 and is the second most common CDG disease subtype after PMM2-CDG (CDG-1a) (Imbach et al. 1999). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency.Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-232.4.1Defective ALG6 does not add glucose to the N-glycan precursorDefective ALG6 does not add glucose to the N-glycan precursorDolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG6) normally adds the first glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins (Imbach et al. 1999). Defects in ALG6 can cause congenital disorder of glycosylation 1c (ALG6-CDG, CDG-1c; MIM:603147), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Imbach et al. 1999, Imbach et al. 2000, Westphal et al. 2000, Sun et al. 2005). ALG6 deficiency is accompanied by an accumulation of the N-glycan precursor (GlcNAc)2 (Man)9 (PP-Dol)1 (Imbach et al. 1999). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Mutations that can cause ALG6-CDG are A333V and S478P. The A333V mutation is the most commom mutation seen in ALG6-CDG patients. These mutations result in altered activity of ALG6 but don't completely abolish its activity (Imbach et al. 1999, Imbach et al. 2000, Dercksen et al. 2013). A c.257+5G>A splice site mutation (not shown here) that causes exon 3 skipping leads to a nonfunctional protein (Imbach et al. 2000, Westphal et al. 2000). Two more mutations can cause the build up of the N-glycan precursor (GlcNAc)2 (Man)9 (PP-Dol)1; a three bp deletion (897-899delAAT) in exon 9 and an intronic<br>mutation (680+2T>G) in intron 7 (neither shown here). Transduction of patient fibroblasts with a lentivirus carrying wildtype hALG6 improved the biochemical phenotype of the cells, confirming that these two mutations are disease-causing (Sun et al. 2005).Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-23Reactome DB_ID: 4493711integral component of lumenal side of endoplasmic reticulum membraneGO0071556alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:37637]alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)Reactomehttp://www.reactome.orgChEBI37637Reactome DB_ID: 5325421dolichyl beta-D-glucosyl phosphate [ChEBI:15812]dolichyl beta-D-glucosyl phosphateChEBI15812PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4724300endoplasmic reticulum membraneGO0005789ALG6 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG6 S478P [endoplasmic reticulum membrane]ALG6 A333V [endoplasmic reticulum membrane]Homo sapiensNCBI Taxonomy9606UniProtQ9Y672GO0004583GO molecular functionReactome Database ID Release 739631762Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631762Reactome Database ID Release 734724291Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4724291ReactomeR-HSA-47242912Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4724291.210924277Pubmed2000Analysis of multiple mutations in the hALG6 gene in a patient with congenital disorder of glycosylation IcWestphal, VSchottstädt, CMarquardt, TFreeze, H HMol. Genet. Metab. 70:219-2323430515Pubmed2013ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel PatientsDercksen, MCrutchley, A CHoney, E MLippert, M MMatthijs, GMienie, L JSchuman, H CVorster, B CJaeken, JJIMD Rep 8:17-2316007612Pubmed2005Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patientSun, LEklund, EAVan Hove, JLFreeze, HHThomas, JAAm J Med Genet A 137:22-610914684Pubmed2000Multi-allelic origin of congenital disorder of glycosylation (CDG)-IcImbach, TGrünewald, SSchenk, BBurda, PSchollen, EWevers, R AJaeken, Jde Klerk, J BBerger, E GMatthijs, GAebi, MHennet, THum. Genet. 106:538-4510359825Pubmed1999A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-IcImbach, TBurda, PKuhnert, PWevers, RAAebi, MBerger, EGHennet, TProc Natl Acad Sci U S A 96:6982-7Reactome Database ID Release 734724289Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4724289ReactomeR-HSA-47242891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4724289.1Defective ALG3 causes ALG3-CDG (CDG-1d)Defective ALG3 causes ALG3-CDG (CDG-1d)Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase (ALG3) adds the sixth mannose (although the first to be derived from dolichyl-phosphate-mannose, DOLPman) to the lipid-linked oligosaccharide (LLO) intermediate GlcNAc(2) Man(5) (PPDol)1 (Korner et al. 1999). Defects in ALG3 are associated with congenital disorder of glycosylation 1d (ALG3-CDG, CDG1d; MIM:601110), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Sun et al. 2005).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-212.4.1Defective ALG3 does not add mannose to the N-glycan precursorDefective ALG3 does not add mannose to the N-glycan precursorDol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase (ALG3) adds the sixth mannose (although the first to be derived from dolichyl-phosphate-mannose, DOLPman) to the lipid-linked oligosaccharide intermediate GlcNAc(2) Man(5) (PPDol)1 (Korner et al. 1999). Defects in ALG3 are associated with congenital disorder of glycosylation 1d (ALG3-CDG, CDG1d; MIM:601110), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. (Sun et al. 2005). Point mutations that cause ALG3-CDG are G118D, R171Q, W71R and M157K (Korner et al. 1999, Sun et al. 2005, Kranz et al. 2007).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21Reactome DB_ID: 4492291dolichyl D-mannosyl phosphate [ChEBI:15809]dolichyl D-mannosyl phosphateDolichyl phosphate D-mannoseChEBI15809Reactome DB_ID: 4492981glycan G00006 [ChEBI:53022]glycan G00006ChEBI53022PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4720485ALG3 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG3 G118D [endoplasmic reticulum membrane]ALG3 M157K [endoplasmic reticulum membrane]ALG3 R171Q [endoplasmic reticulum membrane]ALG3 W71R [endoplasmic reticulum membrane]UniProtQ92685GO0000033GO molecular functionReactome Database ID Release 739631799Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631799Reactome Database ID Release 734720473Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4720473ReactomeR-HSA-47204732Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4720473.217551933Pubmed2007CDG-Id in two siblings with partially different phenotypesKranz, ChristianSun, LiangwuEklund, Erik AKrasnewich, DonnaCasey, Janet RFreeze, Hudson HAm. J. Med. Genet. A 143:1414-2015840742Pubmed2005Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasiaSun, LEklund, EAChung, WKWang, CCohen, JFreeze, HHJ Clin Endocrinol Metab 90:4371-510581255Pubmed1999Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferaseKörner, CKnauer, RStephani, UMarquardt, TLehle, Lvon Figura, KEMBO J. 18:6816-22Reactome Database ID Release 734720475Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4720475ReactomeR-HSA-47204751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4720475.1Defective MPDU1 causes MPDU1-CDG (CDG-1f)Defective MPDU1 causes MPDU1-CDG (CDG-1f)Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15Defective MPDU1 does not promote transfer of Man to N-glycan precursor (GlcNAc)2 (Man)7 (PP-Dol)1 by ALG12Defective MPDU1 does not promote transfer of Man to N-glycan precursor (GlcNAc)2 (Man)7 (PP-Dol)1 by ALG12Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15Reactome DB_ID: 4492291Reactome DB_ID: 4493121alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:59088]alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBI59088Reactome Database ID Release 734686998Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4686998ReactomeR-HSA-46869983Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4686998.311733564Pubmed2001MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type IfSchenk, BImbach, TFrank, C GGrubenmann, C ERaymond, G VHurvitz, HKorn-Lubetzki, IRevel-Vik, SRaas-Rotschild, ALuder, A SJaeken, JBerger, E GMatthijs, GHennet, TAebi, MJ. Clin. Invest. 108:1687-9511179430Pubmed2001Requirement of the Lec35 gene for all known classes of monosaccharide-P-dolichol-dependent glycosyltransferase reactions in mammalsAnand, MRush, J SRay, SDoucey, M AWeik, JWare, F EHofsteenge, JWaechter, C JLehrman, M AMol. Biol. Cell 12:487-50111733556Pubmed2001A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If)Kranz, CDenecke, JLehrman, M ARay, SKienz, PKreissel, GSagi, DPeter-Katalinic, JFreeze, H HSchmid, TJackowski-Dohrmann, SHarms, EMarquardt, TJ. Clin. Invest. 108:1613-9ACTIVATIONReactome Database ID Release 739631845Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631845Converted from EntitySet in ReactomeReactome DB_ID: 4717371MPDU1 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMPDU1 L74S [endoplasmic reticulum membrane]MPDU1 G73E [endoplasmic reticulum membrane]MPDU1 L119P [endoplasmic reticulum membrane]MPDU1 L171Sfs*42 [endoplasmic reticulum membrane]MPDU1 M1T [endoplasmic reticulum membrane]UniProtO75352Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)8 (PP-Dol)1 by ALG9Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)8 (PP-Dol)1 by ALG9Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15Reactome DB_ID: 4492291Reactome DB_ID: 4493651alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->3)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:59091]alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->3)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBI59091Reactome Database ID Release 739036020Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9036020ReactomeR-HSA-90360202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9036020.2ACTIVATIONReactome Database ID Release 739631911Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631911Converted from EntitySet in ReactomeReactome DB_ID: 4717371Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)6 (PP-Dol)1 by ALG9Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)6 (PP-Dol)1 by ALG9Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15Reactome DB_ID: 4492291Reactome DB_ID: 4493151glycan G10595 [ChEBI:53023]glycan G10595ChEBI53023Reactome Database ID Release 739036021Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9036021ReactomeR-HSA-90360212Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9036021.2ACTIVATIONReactome Database ID Release 739631732Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631732Converted from EntitySet in ReactomeReactome DB_ID: 4717371Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)5 (PP-Dol)1 by ALG3Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)5 (PP-Dol)1 by ALG3Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).Authored: Jassal, B, 2013-10-15Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-15Reactome DB_ID: 4492291Reactome DB_ID: 4492981Reactome Database ID Release 739036025Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9036025ReactomeR-HSA-90360252Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9036025.2ACTIVATIONReactome Database ID Release 739631953Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631953Converted from EntitySet in ReactomeReactome DB_ID: 4717371Reactome Database ID Release 734687000Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4687000ReactomeR-HSA-46870002Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4687000.2Defective ALG12 causes ALG12-CDG (CDG-1g)Defective ALG12 causes ALG12-CDG (CDG-1g)Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase (ALG12) (Chantret et al. 2002) normally tranfers the 8th mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG12 are associated with congenital disorder of glycosylation 1g (ALG12-CDG, CDG1g; MIM:607143), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Chantret et al. 2002, Grubenmann et al. 2002). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency.Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-212.4.1Defective ALG12 does not add mannose to the N-glycan precursorDefective ALG12 does not add mannose to the N-glycan precursorDol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase (ALG12) (Chantret et al. 2002) normally tranfers the 8th mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG12 are associated with congenital disorder of glycosylation 1g (ALG12-CDG, CDG1g; MIM:607143), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Chantret et al. 2002, Grubenmann et al. 2002). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Point mutations that can cause ALG12-CDG are F142V, T67M, R146Q, G101R, L158P and Y414* (Chantret et al. 2002, Grubenmann et al. 2002).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21Reactome DB_ID: 4492291Reactome DB_ID: 4493121PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4722114ALG12 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG12 T67M [endoplasmic reticulum membrane]ALG12 L158P [endoplasmic reticulum membrane]ALG12 R146Q [endoplasmic reticulum membrane]ALG12 G101R [endoplasmic reticulum membrane]ALG12 Y414* [endoplasmic reticulum membrane]ALG12 F142V [endoplasmic reticulum membrane]UniProtQ9BV10GO0000030GO molecular functionReactome Database ID Release 739631930Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631930Reactome Database ID Release 734720497Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4720497ReactomeR-HSA-47204972Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4720497.212217961Pubmed2002ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lgGrubenmann, Claudia EFrank, Christian GKjaergaard, SusanneBerger, Eric GAebi, MHennet, ThierryHum. Mol. Genet. 11:2331-911983712Pubmed2002Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferaseChantret, IDupré, TDelenda, CBucher, SDancourt, JBarnier, ACharollais, AHeron, DBader-Meunier, BDanos, OSeta, NDurand, GOriol, RCodogno, PMoore, SEJ Biol Chem 277:25815-22Reactome Database ID Release 734720489Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4720489ReactomeR-HSA-47204891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4720489.1Defective ALG8 causes ALG8-CDG (CDG-1h)Defective ALG8 causes ALG8-CDG (CDG-1h)The probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG8) (Stanchi et al. 2001, Chantret et al. 2003) normally adds the second glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG8 can cause congenital disorder of glycosylation 1h (ALG8-CDG, CDG-1h; MIM:608104), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Chantret et al. 2003, Schollen et al. 2004). ALG8 deficiency is accompanied by an accumulation of the N-glycan precursor (Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency.Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-232.4.1Defective ALG8 does not add glucose to the N-glycan precursorDefective ALG8 does not add glucose to the N-glycan precursorThe probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase (ALG8) (Chantret et al. 2003) normally adds the second glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG8 can cause congenital disorder of glycosylation 1h (ALG8-CDG, CDG-1h; MIM:608104), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Chantret et al. 2003, Schollen et al. 2004). ALG8 deficiency is accompanied by an accumulation of the N-glycan precursor (Glc)1 (GlcNAc)2 (Man)9 (PP-Dol)1. Mutations that can cause ALG8-CDG include T47P, G275D, V133Sfs*3 and T138Kfs*19 (Chantret et al. 2003, Schollen et al. 2004).Authored: Jassal, B, 2013-10-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-23Reactome DB_ID: 5325421Reactome DB_ID: 4496491alpha-Gal-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol) [ChEBI:59081]alpha-Gal-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-alpha-GlcNAc(PP-Dol)ChEBI59081PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4724315ALG8 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG8 T138Kfs*19 [endoplasmic reticulum membrane]ALG8 G275D [endoplasmic reticulum membrane]ALG8 T47P [endoplasmic reticulum membrane]ALG8 V133Sfs*3 [endoplasmic reticulum membrane]UniProtQ9BVK2Reactome Database ID Release 739631887Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631887Reactome Database ID Release 734724330Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4724330ReactomeR-HSA-47243302Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4724330.215235028Pubmed2004Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency)Schollen, EFrank, CGKeldermans, LReyntjens, RGrubenmann, CEClayton, Peter TWinchester, BGSmeitink, JWevers, RAAebi, MHennet, TMatthijs, GJ Med Genet 41:550-612480927Pubmed2003A deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylationChantret, IsabelleDancourt, JuliaDupré, ThierryDelenda, ChristopheBucher, StéphanieVuillaumier-Barrot, SandrineOgier de Baulny, HélènePeletan, CelineDanos, OlivierSeta, NathalieDurand, GenevièveOriol, RafaelCodogno, PatriceMoore, Stuart E HJ. Biol. Chem. 278:9962-71Reactome Database ID Release 734724325Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4724325ReactomeR-HSA-47243251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4724325.111124703Pubmed2001Characterization of 16 novel human genes showing high similarity to yeast sequencesStanchi, FBertocco, EToppo, SDioguardi, RSimionati, BCannata, NZimbello, RLanfranchi, GValle, GYeast 18:69-80Defective ALG2 causes ALG2-CDG (CDG-1i)Defective ALG2 causes ALG2-CDG (CDG-1i)Alpha 1,3/1,6 mannosyltransferase ALG2 (ALG2) is a bifunctional mannosyltransferase normally tranfers a mannose moiety to the lipid linked oligosaccharide (LLO aka N glycan precursor) which is required for subsequent N glycosylation of proteins. Defects in ALG2 can cause congenital disorder of glycosylation 1i (ALG2-CDG, previously known as CDG1i; MIM:607906), a multisystem disorder characterised by under glycosylated serum glycoproteins. CDG type 1 diseases result in a wide phenotypic spectrum, from poor neurological development, psychomotor retardation and dysmorphic features to hypotonia, coagulation abnormalities and immunodeficiency (Thiel et al. 2003). Defect in ALG2 can also cause congenital myasthenic syndrome (ALG2-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al. 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG2-CMS include p.V68G and p.72_75delinsSPR (Cossins et al. 2013). Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-122.4.1Defective ALG2 does not transfer a second Man to N-glycan precursorDefective ALG2 does not transfer a second Man to N-glycan precursorAlpha 1,3/1,6 mannosyltransferase ALG2 (ALG2) is a bifunctional mannosyltransferase which normally transfers a mannose moiety to the lipid linked oligosaccharide (LLO aka N glycan precursor) which is required for subsequent N glycosylation of proteins. Defects in ALG2 can cause congenital disorder of glycosylation 1i (ALG2-CDG, previously known as CDG1i; MIM:607906), a multisystem disorder characterised by under glycosylated serum glycoproteins. Two mutations causing ALG2-CDG have been identified in a patient; a compound heterozygote where one mutation is a 1-bp deletion (G) at 1040 (p.G347Vfs*27) and the other a G-T transversion at 393 (not shown) (Thiel et al. 2003). Defect in ALG2 can also cause congenital myasthenic syndrome (ALG2-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al., 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG2-CMS include p.V68G and p.72_75delinsSPR (Cossins et al., 2013).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12Reactome DB_ID: 4492831integral component of cytoplasmic side of endoplasmic reticulum membraneGO0071458beta-D-mannosyldiacetylchitobiosyldiphosphodolichol [ChEBI:18396]beta-D-mannosyldiacetylchitobiosyldiphosphodolicholChEBI18396Reactome DB_ID: 1628601cytosolGO0005829GDP-alpha-D-mannose [ChEBI:15820]GDP-alpha-D-mannoseChEBI15820PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 5633219ALG2 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG2 G347Vfs*27 [endoplasmic reticulum membrane]ALG2 V68G [endoplasmic reticulum membrane]ALG2 72-75delinsSPR [endoplasmic reticulum membrane]UniProtQ9H553Reactome Database ID Release 739631942Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631942Reactome Database ID Release 734549368Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4549368ReactomeR-HSA-45493682Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4549368.212684507Pubmed2003A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesisThiel, CSchwarz, MPeng, JGrzmil, MHasilik, MBraulke, TKohlschütter, Avon Figura, KLehle, LKörner, CJ Biol Chem 278:22498-505Reactome Database ID Release 734549349Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4549349ReactomeR-HSA-45493491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4549349.123404334Pubmed2013Congenital myasthenic syndromes due to mutations in ALG2 and ALG14Cossins, JudithBelaya, KatsiarynaHicks, DebbieSalih, Mustafa AFinlayson, SarahCarboni, NicolaLiu, Wei WeiMaxwell, SusanZoltowska, KatarzynaFarsani, Golara TorabiLaval, StevenSeidhamed, Mohammed ZainBrain 136:944-56Defective DPAGT1 causes DPAGT1-CDG (CDG-1j) and CMSTA2Defective DPAGT1 causes DPAGT1-CDG (CDG-1j) and CMSTA2UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the initial committed step in the biosynthesis of dolichyl pyrophosphate-oligosaccharides. Defects in DPAGT1 cause congenital disorder of glycosylation 1j (DPAGT1-CDG, previously known as CDG-1j; MIM:608093), a multisystem disorder characterised by under-glycosylated serum glycoproteins (Wu et al. 2003, Timal et al. 2012). Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Defects in DPAGT1 can also cause myasthenic syndrome, congenital, with tubular aggregates, 2 (CMSTA2; MIM:614750), characterised by muscle weakness of mainly the proximal limb muscles, with tubular aggregates present on muscle biopsy. Sufferers find walking difficult and fall frequently. Younger sufferers show hypotonia and poor head control. A disorder of neuromuscular transmission is detected on electromyography (Belaya et al. 2012, Finlayson et al. 2013).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-122.7.8.15Defective DPAGT1 does not transfer GlcNAc to DOLPDefective DPAGT1 does not transfer GlcNAc to DOLPIn the first committed step of N-glycan precursor (LLO) synthesis, UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) normally catalyses the transfer of N-acetylglucosamine (GlcNAc), via an alpha-1,3 linkage, to a molecule of dolichyl phosphate (DOLP). Defects in DPAGT1 can cause congenital disorder of glycosylation, type 1j (DPAGT1-CDG, previously called CDG1j; MIM:608093), a multisystem disorder characterised by under-glycosylated serum glycoproteins. Clinical features include defective nervous system development, psychomotor retardation, coagulation diorders and immunodeficiency. Mutations causing DPAGT1-CDG include Y170C, I69N and a G-A transition in intron 1 (not shown here) which results in degradation of the mutant mRNA (Wu et al. 2003, Timal et al. 2012). Defects in DPAGT1 can also cause myasthenic syndrome, congenital, with tubular aggregates, 2 (CMSTA2; MIM:614750 a syndrome that arises from impaired neuromuscular transmission and characterised by muscle weakness, especially of the limb-girdle. Mutations causing CMSTA2 include V117I, M108I, L120M, T234Hfs*116 and V264G (Belaya et al. 2012). Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12Reactome DB_ID: 4492991dolichyl phosphate [ChEBI:16214]dolichyl phosphatedolichol monophosphateDolichyl monophosphateDolichol phosphateChEBI16214Reactome DB_ID: 1627561UDP-N-acetyl-alpha-D-glucosamine [ChEBI:16264]UDP-N-acetyl-alpha-D-glucosamineChEBI16264PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4549346DPAGT1 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDPAGT1 T234Hfs*116 [endoplasmic reticulum membrane]DPAGT1 M108I [endoplasmic reticulum membrane]DPAGT1 V264G [endoplasmic reticulum membrane]DPAGT1 I65N [endoplasmic reticulum membrane]DPAGT1 L120M [endoplasmic reticulum membrane]DPAGT1 V117I [endoplasmic reticulum membrane]DPAGT1 Y170C [endoplasmic reticulum membrane]UniProtQ9H3H5GO0003975GO molecular functionReactome Database ID Release 739631918Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631918Reactome Database ID Release 734549334Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4549334ReactomeR-HSA-45493342Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4549334.212872255Pubmed2003Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type IjWu, XRush, JSKaraoglu, DKrasnewich, DLubinsky, MSWaechter, CJGilmore, RFreeze, HHHum Mutat 22:144-5022492991Pubmed2012Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencingTimal, SharitaHoischen, AlexanderLehle, LudwigAdamowicz, MaciejHuijben, KarinSykut-Cegielska, JolantaPaprocka, JustynaJamroz, Ewavan Spronsen, Francjan JKörner, ChristianGilissen, ChristianRodenburg, Richard JEidhof, IlseVan den Heuvel, LambertThiel, ChristianWevers, RAMorava, EvaVeltman, JorisLefeber, Dirk JHum. Mol. Genet. 21:4151-6122742743Pubmed2012Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregatesBelaya, KatsiarynaFinlayson, SarahSlater, Clarke RCossins, JudithLiu, Wei WeiMaxwell, SusanMcGowan, SJMaslau, SiarheiTwigg, SRWalls, Timothy JPascual Pascual, Samuel IPalace, JacquelineBeeson, DavidAm. J. Hum. Genet. 91:193-201Reactome Database ID Release 734549356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4549356ReactomeR-HSA-45493561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4549356.123447650Pubmed2013Clinical features of congenital myasthenic syndrome due to mutations in DPAGT1Finlayson, SarahPalace, JacquelineBelaya, KatsiarynaWalls, Timothy JNorwood, FionaBurke, GeorginaHolton, Janice LPascual-Pascual, Samuel ICossins, JudithBeeson, DavidJ. Neurol. Neurosurg. Psychiatr. 84:1119-25Defective ALG1 causes ALG1-CDG (CDG-1k)Defective ALG1 causes ALG1-CDG (CDG-1k)Chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) normally tranfers a mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG1 can cause congenital disorder of glycosylation 1k (ALG1-CDG, previously known as CDG1k; MIM:608540), a multisystem disorder characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Compared to other CDGs, ALG1-CDG has a very severe phenotype, which can result in an early death (Schwarz et al. 2004, Kranz et al. 2004, Dupre et al. 2010).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-122.4.1.142Defective ALG1 does not transfer the first Man to the N-glycan precursorDefective ALG1 does not transfer the first Man to the N-glycan precursorChitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) normally tranfers a mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG1 can cause congenital disorder of glycosylation 1k (ALG1-CDG, previously known as CDG1k; MIM:608540), a multisystem disorder characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Compared to other CDGs, ALG1-CDG has a very severe phenotype, which can result in an early death. Mutations in ALG1 causing ALG1-CDG include S258L, G342P, S150R, M377V, G145D, C396* and R276W (Schwarz et al. 2004, Kranz et al. 2004, Grubenmann et al. 2004, Dupre et al. 2010).Authored: Jassal, B, 2013-09-12Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-12Reactome DB_ID: 1628601Reactome DB_ID: 4492931diacetylchitobiosyldiphosphodolichol [ChEBI:18341]diacetylchitobiosyldiphosphodolicholChEBI18341PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4549394ALG1 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG1 C396* [endoplasmic reticulum membrane]ALG1 G145D [endoplasmic reticulum membrane]ALG1 R276W [endoplasmic reticulum membrane]ALG1 E342P [endoplasmic reticulum membrane]ALG1 S258L [endoplasmic reticulum membrane]ALG1 M377V [endoplasmic reticulum membrane]ALG1 S150R [endoplasmic reticulum membrane]UniProtQ9BT22GO0004578GO molecular functionReactome Database ID Release 739631741Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631741Reactome Database ID Release 734549382Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4549382ReactomeR-HSA-45493822Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4549382.214973782Pubmed2004Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase IKranz, CDenecke, JLehle, LSohlbach, KJeske, SMeinhardt, FRossi, RGudowius, SMarquardt, TAm J Hum Genet 74:545-5114973778Pubmed2004Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type IkSchwarz, MThiel, CLübbehusen, JDorland, Bde Koning, Tvon Figura, KLehle, LKörner, CAm J Hum Genet 74:472-8120679665Pubmed2010Guanosine diphosphate-mannose:GlcNAc2-PP-dolichol mannosyltransferase deficiency (congenital disorders of glycosylation type Ik): five new patients and seven novel mutationsDupré, TVuillaumier-Barrot, SChantret, IYayé, H SLe Bizec, CAfenjar, AAltuzarra, CBarnérias, CBurglen, Lde Lonlay, PFeillet, FNapuri, SSeta, NMoore, S E HJ. Med. Genet. 47:729-3514709599Pubmed2004Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type IkGrubenmann, CEFrank, CGHülsmeier, AJSchollen, EMatthijs, GMayatepek, EBerger, EGAebi, MHennet, THum Mol Genet 13:535-42Reactome Database ID Release 734549380Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4549380ReactomeR-HSA-45493801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4549380.1Defective ALG9 causes ALG9-CDG (CDG-1l)Defective ALG9 causes ALG9-CDG (CDG-1l)Alpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-212.4.1Defective ALG9 does not add the seventh mannose to the N-glycan precursorDefective ALG9 does not add the seventh mannose to the N-glycan precursorAlpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004). Point mutations that can cause ALG9-CDG are E523K and Y286C (Frank et al. 2004, Weinstein et al. 2005).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21Reactome DB_ID: 4492291Reactome DB_ID: 4493151PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4720499ALG9 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG9 Y286C [endoplasmic reticulum membrane]ALG9 E523K [endoplasmic reticulum membrane]UniProtQ9H6U8GO0000026GO molecular functionReactome Database ID Release 739631913Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631913Reactome Database ID Release 734720478Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4720478ReactomeR-HSA-47204783Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4720478.315148656Pubmed2004Identification and functional analysis of a defect in the human ALG9 gene: definition of congenital disorder of glycosylation type ILFrank, CGGrubenmann, CEEyaid, WBerger, EGAebi, MHennet, TAm J Hum Genet 75:146-5015945070Pubmed2005CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic featuresWeinstein, MSchollen, EMatthijs, GNeupert, CHennet, TGrubenmann, CEFrank, CGAebi, MClarke, JTGriffiths, ASeargeant, LPoplawski, NAm J Med Genet A 136:194-72.4.1Defective ALG9 does not add the last mannose to the N-glycan precursorDefective ALG9 does not add the last mannose to the N-glycan precursorAlpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004). Point mutations that can cause ALG9-CDG are E523K and Y286C (Frank et al. 2004, Weinstein et al. 2005).Authored: Jassal, B, 2013-10-21Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-21Reactome DB_ID: 4492291Reactome DB_ID: 4493651PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4720499Reactome Database ID Release 739631867Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631867Reactome Database ID Release 739035514Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9035514ReactomeR-HSA-90355142Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9035514.2Reactome Database ID Release 734720454Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4720454ReactomeR-HSA-47204542Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4720454.2Defective RFT1 causes RFT1-CDG (CDG-1n)Defective RFT1 causes RFT1-CDG (CDG-1n)The N-glycan precursor is flipped across the ER membrane, moving it from the cytosolic side to the ER lumenal side. The exact mechanism of this translocation is not well understood but protein RFT1 homolog (RFT1) is known to be involved (Helenius et al. 2002). Defects in RFT1 are associated with congenital disorder of glycosylation 1n (RFT1-CDG, CDG-1n). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Early-onset developmental retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency are reported features of this disorder (Haeuptle et al. 2008).Authored: Jassal, B, 2013-09-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-23Defective RFT1 does not flip the N-glycan precursorDefective RFT1 does not flip the N-glycan precursorThe N-glycan precursor is flipped across the ER membrane, moving it from the cytosolic side to the ER lumenal side. The exact mechanism of this translocation is not well understood but protein RFT1 homolog (RFT1) is known to be involved (Helenius et al. 2002). Defects in RFT1 are associated with congenital disorder of glycosylation 1n (RFT1-CDG, CDG-1n). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Early-onset developmental retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency are reported features of this disorder. In a patient with RFT1-CDG, Haeuptle et al. identified a homozygous C-T transition at nucleotide 199, resulting in a substitution of cysteine for arginine at codon 67 (R67C) (Haeuptle et al. 2008).Authored: Jassal, B, 2013-09-23Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-23Reactome DB_ID: 4493321PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 4570578UniProt:Q96AA3 RFT1RFT1RFT1FUNCTION May be involved in N-linked oligosaccharide assembly. May participate in the translocation of oligosaccharide from the cytoplasmic side to the lumenal side of the endoplasmic reticulum membrane.SIMILARITY Belongs to the RFT1 family.UniProtQ96AA3L-asparagine 67 replaced with L-cysteine67EQUALL-asparagine removal [MOD:01633]Chain Coordinates1EQUAL541EQUALGO0034202GO molecular functionReactome Database ID Release 739631742Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631742Reactome Database ID Release 734570573Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4570573ReactomeR-HSA-45705732Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4570573.211807558Pubmed2002Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 proteinHelenius, JNg, DTMarolda, CLWalter, PValvano, MAAebi, MNature 415:447-5018313027Pubmed2008Human RFT1 deficiency leads to a disorder of N-linked glycosylationHaeuptle, MAPujol, FMNeupert, CWinchester, BKastaniotis, AJAebi, MHennet, TAm J Hum Genet 82:600-6Reactome Database ID Release 734570571Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4570571ReactomeR-HSA-45705711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4570571.1Defective ALG11 causes ALG11-CDG (CDG-1p)Defective ALG11 causes ALG11-CDG (CDG-1p)GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11) transfers the fourth and fifth mannoses (Man) to the N-glycan precursor in an alpha-1,2 orientation. These additions are the last two on the cytosolic side of the ER membrane before the N-glycan is flipped to the luminal side of the membrane. Recently discovered defects in ALG11 have been linked to congential disorder of glycosylation, type 1p (ALG11-CDG, CGD1p) (Rind et al. 2010, Thiel et al. 2012). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Early-onset developmental retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency are reported features of this disorder (Rind et al. 2010, Thiel et al. 2012).Authored: Jassal, B, 2013-09-13Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-132.4.1Defective ALG11 does not transfer Man to the N-glycan precursorDefective ALG11 does not transfer Man to the N-glycan precursorGDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11) transfers the fourth and fifth mannoses (Man) to the N-glycan precursor in an alpha-1,2 orientation. These additions are the last two on the cytosolic side of the ER membrane before the N-glycan is flipped to the luminal side of the membrane. Recently discovered defects in ALG11 have been linked to congential disorder of glycosylation, type 1p (ALG11-CDG, CGD1p) (Rind et al. 2010, Thiel et al. 2012). The disease is a multi-system disorder characterised by under-glycosylated serum glycoproteins. Mutations causing ALG11-CDG include E398K, L381S, L86S, Q318P and Y279S (Rind et al. 2010, Thiel et al. 2012).Authored: Jassal, B, 2013-09-13Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-09-13Reactome DB_ID: 1628602Reactome DB_ID: 4492431alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-2-alpha-D-GlcNAc(PP-Dol) [ChEBI:53742]alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-2-alpha-D-GlcNAc(PP-Dol)ChEBI53742PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4570572ALG11 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG11 L381S [endoplasmic reticulum membrane]ALG11 Q318P [endoplasmic reticulum membrane]ALG11 Y279S [endoplasmic reticulum membrane]ALG11 L86S [endoplasmic reticulum membrane]ALG11 E398K [endoplasmic reticulum membrane]UniProtQ2TAA5Reactome Database ID Release 739631975Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631975Reactome Database ID Release 734551297Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4551297ReactomeR-HSA-45512973Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4551297.322213132Pubmed2012Improved diagnostics lead to identification of three new patients with congenital disorder of glycosylation-IpThiel, ChristianRind, NinaPopovici, DianaHoffmann, GFHanson, KristenConway, Robert LAdamski, Craig RButler, ElizabethScanlon, RhondaLambert, MApeshiotis, NeophytosThiels, CharlotteMatthijs, GertKörner, ChristianHum. Mutat. 33:485-720080937Pubmed2010A severe human metabolic disease caused by deficiency of the endoplasmatic mannosyltransferase hALG11 leads to congenital disorder of glycosylation-IpRind, NinaSchmeiser, VerenaThiel, ChristianAbsmanner, BirgitLübbehusen, JürgenHocks, JuliaApeshiotis, NeophytosWilichowski, EkkehardLehle, LudwigKörner, ChristianHum. Mol. Genet. 19:1413-24Reactome Database ID Release 734551295Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4551295ReactomeR-HSA-45512951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4551295.1Defective MGAT2 causes MGAT2-CDG (CDG-2a)Defective MGAT2 causes MGAT2-CDG (CDG-2a)Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2) normally catalyses the transfer of a GlcNAc moiety onto the alpha-1,6 mannose of an alpha-1,4 branch of oligomannose N-glycans to form complex N-glycans (Tan et al. 1995). Defects in MGAT2 are associated with congenital disorder of glycosylation type IIa (MGAT2-CDG, CDG-2a; MIM:212066), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Tan et al. 1996, Cormier-Daire et al. 2000, Alkuraya 2010, Alazami et al. 2012). Type II CDGs refer to defects in the trimming and processing of protein-bound glycans.Authored: Jassal, B, 2013-10-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-292.4.1.143Defective MGAT2 does not transfer GlcNAc to N-glycansDefective MGAT2 does not transfer GlcNAc to N-glycansAlpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2) normally catalyses the transfer of a GlcNAc moiety onto the alpha,1,6 mannose of an alpha,1,4 branch of oligomannose N-glycans to form complex N-glycans (Tan et al. 1995). Defects in MGAT2 are associated with congenital disorder of glycosylation type IIa (MGAT2-CDG, CDG-2a; MIM:212066), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. Mutations that can cause MGAT2-CDG are S290F, H262R, C339*, N318D and K237N (Tan et al. 1996, Cormier-Daire et al. 2000, Alkuraya 2010, Alazami et al. 2012).Authored: Jassal, B, 2013-10-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 9140031Golgi lumenGO0005796Reactome DB_ID: 9758191N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residue [ChEBI:60615]N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residueChEBI60615PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4839790Golgi membraneGO0000139MGAT2 mutants [Golgi membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMGAT2 C339* [Golgi membrane]MGAT2 K237N [Golgi membrane]MGAT2 H262R [Golgi membrane]MGAT2 N318D [Golgi membrane]MGAT2 S290F [Golgi membrane]UniProtQ10469GO0008455GO molecular functionReactome Database ID Release 739631739Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631739Reactome Database ID Release 734793955Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793955ReactomeR-HSA-47939552Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793955.28808595Pubmed1996Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain developmentTan, JDunn, JJaeken, JSchachter, HAm J Hum Genet 59:810-711228641Pubmed2000Congenital disorders of glycosylation IIa cause growth retardation, mental retardation, and facial dysmorphismCormier-Daire, VAmiel, JVuillaumier-Barrot, STan, JDurand, GMunnich, ALe Merrer, MSeta, NJ. Med. Genet. 37:875-720684000Pubmed2010Mental retardation, growth retardation, unusual nose, and open mouth: an autosomal recessive entityAlkuraya, Fowzan SAm. J. Med. Genet. A 152:2160-322105986Pubmed2012Congenital disorder of glycosylation IIa: the trouble with diagnosing a dysmorphic inborn error of metabolismAlazami, Anas MMonies, DorotaMeyer, Brian FAlzahrani, FatemaHashem, MaisSalih, Mustafa AAlkuraya, Fowzan SAm. J. Med. Genet. A 158:245-67635144Pubmed1995The human UDP-N-acetylglucosamine: alpha-6-D-mannoside-beta-1,2- N-acetylglucosaminyltransferase II gene (MGAT2). Cloning of genomic DNA, localization to chromosome 14q21, expression in insect cells and purification of the recombinant proteinTan, JD'Agostaro, AFBendiak, BReck, FSarkar, MSquire, JALeong, PSchachter, HEur J Biochem 231:317-28Reactome Database ID Release 734793952Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793952ReactomeR-HSA-47939521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793952.1Defective MOGS causes MOGS-CDG (CDG-2b)Defective MOGS causes MOGS-CDG (CDG-2b)After the lipid-linked oligosaccharide (LLO) precursor is attached to the protein, the outer alpha-1,2-linked glucose is removed by by mannosyl-oligosaccharide glucosidase (MOGS). This is a mandatory step for protein folding control and glycan extension. Defects in MOGS are associated with congenital disorder of glycosylation type IIb (CDGIIb), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (De Praeter et al. 2000, Voelker et al. 2002). Type II CDGs refer to defects in the trimming and processing of protein-bound glycans.Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-293.2.1.106Defective MOGS does not cleave glucose from an N-glycosylated proteinDefective MOGS does not cleave glucose from an N-glycosylated proteinAfter the lipid-linked oligosaccharide (LLO) precursor is attached to the protein, the outer alpha-1,2-linked glucose is removed by by mannosyl-oligosaccharide glucosidase (MOGS). This is a mandatory step for protein folding control and glycan extension. Defects in MOGS are associated with congenital disorder of glycosylation type IIb (MOGS-CDG, CDGIIb; MIM:606056), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. Mutations causing MOGS-CDG are R486T and F652L. Kinetic studies using cultured fibroblasts showed that the by mannosyl-oligosaccharide glucosidase activity in the patient's cells was < 1% of control activity (De Praeter et al. 2000, Voelker et al. 2002). Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 5325341endoplasmic reticulum lumenGO0005788unfolded protein:(Glc)3 (GlcNAc)2 (Man)9 (Asn)1 [endoplasmic reticulum lumen]unfolded protein:(Glc)3 (GlcNAc)2 (Man)9 (Asn)1Reactome DB_ID: 5326731N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-L-Asn residue [ChEBI:59084]N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)]-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-L-Asn residueChEBI59084Reactome DB_ID: 3811301unfolded protein [endoplasmic reticulum lumen]unfolded proteinReactome Database ID Release 73532534Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=532534ReactomeR-HSA-5325341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-532534.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4839809MOGS mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMOGS F652L [endoplasmic reticulum membrane]MOGS R486T [endoplasmic reticulum membrane]UniProtQ13724GO0004573GO molecular functionReactome Database ID Release 739631931Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631931Reactome Database ID Release 734793947Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793947ReactomeR-HSA-47939472Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793947.210788335Pubmed2000A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiencyDe Praeter, CMGerwig, GJBause, ENuytinck, LKVliegenthart, JFBreuer, WKamerling, JPEspeel, MFMartin, JJDe Paepe, AMChan, NWDacremont, GAVan Coster, RNAm J Hum Genet 66:1744-5612145188Pubmed2002Processing of N-linked carbohydrate chains in a patient with glucosidase I deficiency (CDG type IIb)Völker, CDe Praeter, CMHardt, BBreuer, WKalz-Füller, BVan Coster, RNBause, EGlycobiology 12:473-83Reactome Database ID Release 734793954Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793954ReactomeR-HSA-47939541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793954.1Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)Congenital disorders of glycosylation (CDG, previously called carbohydrate-deficient glycoprotein syndromes, CDGSs), are a group of hereditary multisystem disorders. They are characterized biochemically by hypoglycosylation of glycoproteins, diagnosed by isoelectric focusing (IEF) of serum transferrin. There are two types of CDG, types I and II. Type I CDG has defects in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. Clinical symptoms are dominated by severe psychomotor and mental retardation, as well as blood coagulation abnormalities (Jaeken 2013). B4GALT1-CDG (CDG type IId) is a multisystem disease, characterized by dysmorphic features, hydrocephalus, hypotonia and blood clotting abnormalities (Hansske et al. 2002).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-292.4.1.38Defective B4GALT1 does not add Gal to N-glycanDefective B4GALT1 does not add Gal to N-glycanThe family of beta 4-galactosyltransferases (B4GALTs) is composed by at least six known members that mediate the transfer of galactose to N-glycan structures and either to begin or elongate keratan chains. Defective B4GALT1 is associated with congenital disorder of glycosylation type IId (B4GALT1-CDG, CDG-2d; MIM:607091), in which clinical symptoms are dominated by dysmorphic features, psychomotor and mental retardation, hypotonia, as well as blood coagulation abnormalities (Hansske et al. 2002). The mutant R345Kfs*6 results in a truncated, inactive polypeptide. Analysis of oligosaccharides from serum transferrin from these patients reveals loss of sialic acid and galactose residues (Hansske et al. 2002).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 7356821UDP-D-galactose [ChEBI:18307]UDP-D-galactoseUDP-D-galactopyranoseUDPgalactoseChEBI18307Reactome DB_ID: 9759101N-glycan [ChEBI:59520]N-glycanChEBI59520PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 3656417UniProt:P15291 B4GALT1B4GALT1B4GALT1GGTB2PATHWAY Protein modification; protein glycosylation.SUBUNIT Homodimer; and heterodimer with alpha-lactalbumin to form lactose synthase. Interacts (via N-terminal cytoplasmic domain) with UBE2Q1 (via N-terminus); the interaction is direct (By similarity).TISSUE SPECIFICITY Ubiquitously expressed, but at very low levels in fetal and adult brain.PTM The soluble form derives from the membrane forms by proteolytic processing.SIMILARITY Belongs to the glycosyltransferase 7 family.UniProtP15291Replacement of residues 345 to 349 by KRQEK1EQUAL349EQUALGO0003831GO molecular functionReactome Database ID Release 739631981Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631981Reactome Database ID Release 734793956Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793956ReactomeR-HSA-47939563Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793956.311901181Pubmed2002Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IIdHansske, BThiel, CLübke, THasilik, MHöning, SPeters, VHeidemann, PHHoffmann, GFBerger, EGvon Figura, KKörner, CJ Clin Invest 109:725-33Reactome Database ID Release 734793953Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793953ReactomeR-HSA-47939531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793953.123622397Pubmed2013Congenital disorders of glycosylationJaeken, JHandb Clin Neurol 113:1737-43Defective MAN1B1 causes MRT15Defective MAN1B1 causes MRT15Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycoyslated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-293.2.1.113Defective MAN1B1 does not hydrolyse 1,2-linked mannose (a branch)Defective MAN1B1 does not hydrolyse 1,2-linked mannose (a branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011). Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 9122831endoplasmic reticulum quality control compartmentGO0044322(un)folded protein:(GlcNAc)2 (Man)9 [endoplasmic reticulum quality control compartment](un)folded protein:(GlcNAc)2 (Man)9Reactome DB_ID: 9122961unfolded protein [endoplasmic reticulum quality control compartment]unfolded proteinReactome DB_ID: 9122881N-{alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->2)]-alpha-Man-(1->3)]-beta-Man-(1->4)-beta-GlcnAc-(1->4)-beta-GlcNAc}-L-Asn residue [ChEBI:59092]N-{alpha-Man-(1->3)-[alpha-Man-(1->2)-alpha-Man-(1->6)]-alpha-Man-(1->6)-[alpha-Man-(1->6)-[alpha-Man-(1->2)-alpha-Man-(1->2)]-alpha-Man-(1->3)]-beta-Man-(1->4)-beta-GlcnAc-(1->4)-beta-GlcNAc}-L-Asn residueChEBI59092Reactome Database ID Release 73912283Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=912283ReactomeR-HSA-9122831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-912283.1Reactome DB_ID: 67818701water [ChEBI:15377]waterChEBI15377PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4960920MAN1B1 mutants [endoplasmic reticulum quality control compartment]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMAN1B1 R334C [endoplasmic reticulum quality control compartment]MAN1B1 W473* [endoplasmic reticulum quality control compartment]MAN1B1 E397K [endoplasmic reticulum quality control compartment]UniProtQ9UKM7GO0004571GO molecular functionReactome Database ID Release 739631749Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631749Reactome Database ID Release 734793949Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793949ReactomeR-HSA-47939493Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793949.320345473Pubmed2010Mapping of three novel loci for non-syndromic autosomal recessive mental retardation (NS-ARMR) in consanguineous families from PakistanRafiq, M AAnsar, MMarshall, C RNoor, AShaheen, NMowjoodi, AKhan, M AAli, GAmin-ud-Din, MFeuk, LVincent, J BScherer, S WClin. Genet. 78:478-8321763484Pubmed2011Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disabilityRafiq, Muhammad ArshadKuss, Andreas WPuettmann, LuciaNoor, AbdulRamiah, AnnapooraniAli, GhazanfarHu, HaoKerio, Nadir AliXiang, YongGarshasbi, MasoudKhan, Muzammil AhmadIshak, Gisele EWeksberg, RosannaUllmann, ReinhardTzschach, AndreasKahrizi, KimiaMahmood, KhalidNaeem, FarooqAyub, MuhammadMoremen, Kelley WVincent, John BRopers, Hans HilgerAnsar, MuhammadNajmabadi, HosseinAm. J. Hum. Genet. 89:176-823.2.1.113Defective MAN1B1 does not hydrolyse a second 1,2-linked mannose (a branch)Defective MAN1B1 does not hydrolyse a second 1,2-linked mannose (a branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 67818701Reactome DB_ID: 9122851unfolded protein:(GlcNAc)2 (Man)8a [endoplasmic reticulum quality control compartment]unfolded protein:(GlcNAc)2 (Man)8aReactome DB_ID: 9122961Reactome DB_ID: 9122981N(4)-{alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residue [ChEBI:60627]N(4)-{alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-Asn residueChEBI60627Reactome Database ID Release 73912285Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=912285ReactomeR-HSA-9122851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-912285.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4960920Reactome Database ID Release 739631832Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631832Reactome Database ID Release 739036008Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9036008ReactomeR-HSA-90360082Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9036008.23.2.1.113Defective MAN1B1 does not hydrolyse 1,2-linked mannose (b branch)Defective MAN1B1 does not hydrolyse 1,2-linked mannose (b branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 9122831Reactome DB_ID: 67818701PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4960920Reactome Database ID Release 739631736Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631736Reactome Database ID Release 739036011Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9036011ReactomeR-HSA-90360112Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9036011.23.2.1.113Defective MAN1B1 does not hydrolyse 1,2-linked mannose (c branch)Defective MAN1B1 does not hydrolyse 1,2-linked mannose (c branch)Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1) normally trims single mannose residues from misfolded glycoproteins, targeting them for degradation and thus providing a quality control process for N-glycosylated proteins. Defects in MAN1B1 can cause mental retardation, autosomal recessive 15 (MRT15; MIM:614202), a disorder resulting in nonsyndromic moderate to severe mental retardation. It is characterised by significantly below average intellectual functioning associated with impaired adaptative behaviour during the developmental period (Rafiq et al. 2010, Rafiq et al. 2011). Mutations that can cause MRT15 are E397K, W473* and R334C (Rafiq et al. 2010, Rafiq et al. 2011).Authored: Jassal, B, 2013-07-29Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, B, 2013-10-29Reactome DB_ID: 9122831Reactome DB_ID: 67818701PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 4960920Reactome Database ID Release 739631798Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631798Reactome Database ID Release 739036012Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9036012ReactomeR-HSA-90360122Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9036012.2Reactome Database ID Release 734793950Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4793950ReactomeR-HSA-47939502Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-4793950.2Defective ALG14 causes congenital myasthenic syndrome (ALG14-CMS)Defective ALG14 causes congenital myasthenic syndrome (ALG14-CMS)UDP-N-acetylglucosamine transferase subunit ALG14 homolog (ALG14) forms a complex with ALG13 protein and is required for the addition of the second N-acetylglucosamine (GlcNAc) to the lipid linked oligosaccharide (LLO) intermediate (GlcNAcDOLDP) (Gao et al. 2005). Defects in ALG14 can cause congenital myasthenic syndrome (ALG14-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al. 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG14-CMS include p.P65L and p.R104* (Cossins et al. 2013).Authored: Jassal, Bijay, 2014-10-31Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, Bijay, 2014-10-312.4.1.141Defective ALG14 does not transfer GlcNAc from UDP-GlcNAc to GlcNAcDOLPDefective ALG14 does not transfer GlcNAc from UDP-GlcNAc to GlcNAcDOLPUDP-N-acetylglucosamine transferase subunit ALG14 homolog (ALG14) forms a complex with ALG13 protein and is required for the addition of the second N-acetylglucosamine (GlcNAc) to the lipid linked oligosaccharide (LLO) intermediate (GlcNAcDOLDP) (Gao et al. 2005). Defects in ALG14 can cause congenital myasthenic syndrome (ALG14-CMS), which is due to a defect in neuromuscular signal transmission (Cossins et al. 2013). The most commonly affected muscles include proximal limb muscles. Mutations causing ALG14-CMS include p.P65L and p.R104* (Cossins et al. 2013).Authored: Jassal, Bijay, 2014-10-31Reviewed: Belaya, Katsiaryna, 2014-10-31Edited: Jassal, Bijay, 2014-10-31Reactome DB_ID: 4492221N-acetyl-D-glucosaminyldiphosphodolichol [ChEBI:18278]N-acetyl-D-glucosaminyldiphosphodolicholChEBI18278Reactome DB_ID: 1627561PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 5633244ALG13:ALG14 mutants [endoplasmic reticulum membrane]ALG13:ALG14 mutantsConverted from EntitySet in ReactomeReactome DB_ID: 56332381ALG14 mutants [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityALG14 P65L [endoplasmic reticulum membrane]ALG14 R104* [endoplasmic reticulum membrane]UniProtQ96F25Reactome DB_ID: 4493291UniProt:Q9NP73 ALG13ALG13GLT28D1CXorf45ALG13MDS031SUBUNIT Isoform 2 may interact with ALG14.DOMAIN Contains 1 OTU domain with intact active sites. No deubiquitinase activity has been detected when tested (PubMed:23827681).SIMILARITY Belongs to the glycosyltransferase 28 family.UniProtQ9NP731EQUAL165EQUALReactome Database ID Release 735633244Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5633244ReactomeR-HSA-56332441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5633244.1GO0004577GO molecular functionReactome Database ID Release 739631825Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9631825Reactome Database ID Release 735633241Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5633241ReactomeR-HSA-56332412Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5633241.216100110Pubmed2005Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form a novel bipartite UDP-N-acetylglucosamine transferase required for the second step of N-linked glycosylationGao, XDTachikawa, HSato, TJigami, YDean, NJ Biol Chem 280:36254-62Reactome Database ID Release 735633231Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5633231ReactomeR-HSA-56332312Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5633231.2Reactome Database ID Release 733781860Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3781860ReactomeR-HSA-37818601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3781860.112409504Pubmed2002Congenital disorders of glycosylation: a reviewGrunewald, StephanieMatthijs, GertJaeken, JaakPediatr. Res. 52:618-2423730680Pubmed2013Congenital disorders of glycosylation. Part I. Defects of protein N-glycosylationCylwik, BogdanNaklicki, MarcinChrostek, LechGruszewska, EwaActa Biochim. Pol. 60:151-6122343051Pubmed2012Diseases of glycosylation beyond classical congenital disorders of glycosylationHennet, ThierryBiochim. Biophys. Acta 1820:1306-1712756558Pubmed2003Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapiesMarquardt, TDenecke, JEur. J. Pediatr. 162:359-79